Annotation of CYP3A5 poor metabolizers

CYP3A5 poor metabolizer is associated with decreased concentrations of maraviroc in people with HIV Infections as compared to CYP3A5 normal metabolizer.

In study A4001026, CYP3A5 poor metabolizers had a significant decrease in average maraviroc plasma concentrations compared to extensive metabolizers, contrary to what would be expected. The authors suggest that that this result may have been influenced by a number of variables, including HIV infection, in the study. This significance was lost when the 'black' and 'white' cohorts were analyzed separately. The authors determined this difference in maraviroc concentrations to not be clinically significant.

From Publication

No Clinical Impact of CYP3A5 Gene Polymorphisms on the Pharmacokinetics and/or Efficacy of Maraviroc in Healthy Volunteers and HIV-1-Infected Subjects. Journal of clinical pharmacology. 2019. Vourvahis Manoli et al.
PMID:30192390(opens in new window) PMCID:PMC6586010(opens in new window) DOI:10.1002/jcph.1306(opens in new window)

Gene

CYP3A5

Phenotype Category

Metabolism/PK

Association Significance

The study reports this association is significant

PharmGKB ID

1450371753

Score
More info on scoring

1

Evidence for Clinical Annotations

This annotation has been used as evidence for the following clinical annotations.

    Study Parameters

    1.

    Study type

    clinical trial, retrospective

    Study size

    617

    Association p-value

    = 0.048

    Biogeographical group
    More info on groups

    Multiple groups

    Population description

    Study Cohort: 524 poor metabolizers and 93 extensive metabolizers from study A4001026 (MERIT study).

    2.

    Study type

    clinical trial, retrospective

    Study size

    144

    Association p-value

    = 0.343

    Biogeographical group
    More info on groups

    Unknown. Participants are designated as 'black' but their biogeographical origin is not given.

    Population description

    Study Cohort: 63 poor metabolizers and 81 extensive metabolizers from study A4001026 (MERIT study).

    3.

    Study type

    clinical trial, retrospective

    Study size

    425

    Association p-value

    = 0.606

    Biogeographical group
    More info on groups

    Unknown. Participants were designated as 'white' but their biogeographical origin is not stated.

    Population description

    Study Cohort: 420 poor metabolizers and 5 extensive metabolizers from study A4001026 (MERIT study).

    Note: Alleles in PharmGKB are mapped to the positive chromosomal strand. Therefore, variants in genes on the "minus" strand (eg. VKORC1) are complemented in PharmGKB annotations.

    History

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